double-blind, randomized, placebo-controlled phase 3 study of etanercept in the treatment of psoriatic arthritis and psoriasis

Conditions: Psoriatic Arthritis; Psoriasis

Summary: this was a phase 3, double-blind, placebo-controlled, randomized, multicenter study in subjects with psoriatic arthritis (psa) and psoriasis comprising 3 periods: a 24-week double-blind period, a ≤ 24-week maintenance period, and a 48-week open-label period. during the double-blind period, subjects were randomized equally to 1 of 2 regimens: etanercept 25 mg twice weekly (biw) or placebo, administered subcutaneously (sc). after the week 24 visit, subjects continued on blind-labeled therapy in a maintenance period until all subjects completed the double-blind period. after the maintenance period, all subjects received open-label etanercept 25 mg biw.

previously presented data from 2 double-blind, placebo-controlled trials (protocols 016.0612 \[investigator ind\] and 016.0030 \[immunex ind\]) led to the approval of etanercept for reducing clinical signs and symptoms of psa. one-year radiographic data from protocol 20021630 led to an additional approval of etanercept for inhibiting structural progression in psa. data are used for the following purposes: * to summarize the clinical efficacy and safety results previously described in the 6-month clinical study report and the radiographic results previously described in the 1-year clinical study report. * to show the effect of etanercept on physical function in subjects with psa and psoriasis, as measured by 2 patient-reported outcome measures (disability index of the stanford health assessment questionnaire \[haq\] and medical outcomes study short-form health survey \[sf-36\]). • to present the radiographic results at 2 years from baseline and the final clinical efficacy and safety results during the open-label period of the study.

Eligibility criteria:
inclusion criteria: subjects had to satisfy the following criteria before randomization into the study: * active psa at the time of screening, including ≥ 3 swollen joints and ≥ 3 tender/painful joints. • had ≥ 1 of the following subtypes of psa: distal interphalangeal (dip) involvement; polyarticular arthritis (absence of rheumatoid nodules and presence of psoriasis); arthritis mutilans; asymmetric peripheral arthritis; or ankylosing spondylitis-like. * arthritis had demonstrated an inadequate response to nonsteroidal antiinflammatory drug (nsaid) therapy. * subjects had plaque psoriasis with qualifying target lesion. target lesion was to be ≥ 2 cm in diameter and could not be on the scalp, axilla, or groin. psoriasis was to be stable (ie, not accelerating). * between 18 and 70 years of age. * subjects remaining on concomitant mtx (≤ 25 mg/week) had inadequate disease control in the opinion of the investigator and had been on a stable dose of mtx for 2 months before start of investigational product. subjects were required to maintain a stable dose of mtx throughout the study. * negative serum pregnancy test within 14 days before the first dose of investigational product in all women (except those surgically sterile or ≥ 5 years postmenopausal). * heterosexually active men and women of childbearing potential agreed to use a medically accepted form of contraception throughout the study, including the exclusionary medicine washout period and follow-up period. * serum aspartate transaminase (ast) and serum alanine transaminase (alt) ≤ 2 times laboratory's upper limit of normal; hemoglobin ≥ 8.5 g/dl; platelet count ≥ 125,000/mm3; white blood cell count ≥ 3,500 cells/mm3; and serum creatinine ≤ 2 mg/dl. * negative hiv test. negative test for hepatitis b surface antigen and hepatitis c. * able to reconstitute and self-inject investigational product or have a designee who could do so. * capable of understanding and giving written, voluntary informed consent. exclusion criteria: * guttate or pustular psoriasis. * evidence of skin conditions (eg, eczema) other than psoriasis that would interfere with evaluations of the effect of study medication on psoriasis. * active severe infection within 1 month of investigational product administration. * subjects must be off antibiotics for 1 week before investigational product administration. * previous receipt of etanercept, known antibody to tnf, or experimental metalloproteinase inhibitors (past or current use of minocycline and doxycycline was acceptable). * receipt of investigational drugs or biologics within 4 weeks of the screening visit. * receipt of anti-cd4 or diptheria il-2 fusion protein within the previous 6 months, with a subsequent abnormal absolute t cell count. * psoralen ultraviolet a phototherapy (puva) within 4 weeks of investigational product initiation. ultraviolet b (uvb) phototherapy within 2 weeks of investigational product initiation. * receipt of disease-modifying anti-rheumatic drugs (dmards) other than mtx (eg, hydroxycholorquine, oral or injectable gold, cyclophosphamide, cyclosporine, azathioprine, d-penicillamine, or sulfasalazine) or intra-articular corticosteroids within 4 weeks before the first dose of investigational product. * dose of nsaid greater than the maximum recommended dose in the product information. nsaid dose had to be stable for ≥ 4 weeks before screening evaluation. * concomitant corticosteroids \> 10 mg/day of prednisone (or its equivalent). corticosteroid dose had to be stable for ≥ 4 weeks before screening evaluation. * topical steroids, oral retinoids, topical vitamin a or d analog preparations or anthralin within 14 days of baseline. (exception: topical therapies were permitted on scalp, axillae, and groin but had to be stable throughout trial.) * pregnancy or lactation in women. * significant concurrent medical diseases including: * diabetes mellitus requiring insulin * uncompensated congestive heart failure * myocardial infarction within 12 months of screening visit * unstable or stable angina pectoris * uncontrolled hypertension * severe pulmonary disease (requiring medical or oxygen therapy) * history of cancer (other than resected cutaneous basal or squamous cell carcinoma or in situ cervical cancer) within 5 years of screening visit * hiv positive, hepatitis b surface antigen, or hepatitis c positive * rheumatoid arthritis, systemic lupus, scleroderma, or polymyositis * any condition judged by the subject's physician that would cause this study to be detrimental to the subject * current or history of psychiatric disease that would interfere with ability to comply with the study protocol or give informed consent. * history of alcohol or drug abuse that would interfere with ability to comply with the study protocol.